RENAL N-OXIDATION OF TRIMETHYLAMINE IN THE CHICKEN DURING TUBULAR EXCRETION

The Sperber technique of infusion into the renal portal circulation in chickens was used to investigate in vivo the renal tubular transport and renal metabolism of trimethylamine (TMA). When ‘4C-TMA was infused at a rate of 1 x 1O mol/min the transport efficiency (TE), that is, the tubular excretion of the ‘4C-label relative to excretion of simultaneously infused p-aminohippuric acid, was 0.70. Progressive addition of unlabeled TMA up to infusion rates of 1 x 1O- mol/min produced a progressive fall in the TE of the ‘4C-label. Identification of the ‘4C-label excreted in the urine revealed that approximately 85 % of the infused “C-TMA was excreted by the infused kidney as a single metabolite over the entire range of infusions. By use of the techniques of low-voltage electrophoresis, high-voltage electrophoretic mobility-pH profile, and gas chromatography/mass spectrometry, the renal metabolite was found to be identical with standard ‘4C-trimethylamine oxide (TMAO). At a TMA infusion rate of 1.5 x 10-6 mol/kg/min reaching the infused kidney, the rate at which TMAO was formed and excreted by the kidney was 0.12 x 10 mol per g of kidney per mm. When ‘4C-TMAO was infused into chickens its TE was 0.1 1, which was not evidence for active excretory transport. Infused TMA was almost entirely metabolized in vivo to its N-oxide, TMAO, which then entered the urine. The renal tubular excretion of ‘4C during infusion of ‘4C-TMA was inhibited by the cationic blocker of transport, quinine, and by the anionic blocker of transport, probenecid